title: In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly.
abstract: Profilins are thought to be essential for regulation of actin assembly. However, the functions of profilins in mammalian tissues are not well understood. In mice profilin I is expressed ubiquitously while profilin II is expressed at high levels only in brain. In extracts from mouse brain, profilin I and profilin II can form complexes with regulators of endocytosis, synaptic vesicle recycling and actin assembly. Using mass spectrometry and database searching we characterized a number of ligands for profilin I and profilin II from mouse brain extracts including dynamin I, clathrin, synapsin, Rho-associated coiled-coil kinase, the Rac-associated protein NAP1 and a member of the NSF/sec18 family. In vivo, profilins co-localize with dynamin I and synapsin in axonal and dendritic processes. Our findings strongly suggest that in brain profilin I and profilin II complexes link the actin cytoskeleton and endocytic membrane flow, directing actin and clathrin assembly to distinct membrane domains.
authors.affiliation: Mouse Biology Programme, EMBL, Monterotondo/Rome, Italy. witke@embl-heidelberg.de
authors.forename: W
authors.initials: W
authors.lastname: Witke
authors.forename: A V
authors.initials: AV
authors.lastname: Podtelejnikov
authors.forename: A
authors.initials: A
authors.lastname: Di Nardo
authors.forename: J D
authors.initials: JD
authors.lastname: Sutherland
authors.forename: C B
authors.initials: CB
authors.lastname: Gurniak
authors.forename: C
authors.initials: C
authors.lastname: Dotti
authors.forename: M
authors.initials: M
authors.lastname: Mann
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003285:Contractile Proteins; D034284:Dynamin I; D034281:Dynamins; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D008958:Models, Molecular; D009474:Neurons / Q000378:metabolism; D051304:Profilins; D011485:Protein Binding; D051381:Rats; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000199:Actins; D003285:Contractile Proteins; D008840:Microfilament Proteins; C495739:Pfn1 protein, mouse; C495740:Pfn1 protein, rat; C495742:Pfn2 protein, mouse; C495743:Pfn2 protein, rat; D051304:Profilins; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034281:Dynamins